scholarly journals Activation of Adenosine Monophosphate-Activated Protein Kinase Drives the Aerobic Glycolysis in Hippocampus for Delaying Cognitive Decline Following Electroacupuncture Treatment in APP/PS1 Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Jianhong Li ◽  
Bingxue Zhang ◽  
Weiwei Jia ◽  
Minguang Yang ◽  
Yuhao Zhang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Energy Metabolism ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Chemical Exchange ◽  
Early Stage ◽  
Aerobic Glycolysis ◽  
Adenosine Monophosphate ◽  
Chemical Exchange Saturation Transfer ◽  
Hexokinase Ii

Aerobic glycolysis (AG), an important pathway of glucose metabolism, is dramatically declined in Alzheimer’s disease (AD). AMP-activated protein kinase (AMPK) is a key regulator to maintain the stability of energy metabolism by promoting the process of AG and regulating glucose metabolism. Interestingly, it has been previously reported that electroacupuncture (EA) treatment can improve cognitive function in AD through the enhancement of glucose metabolism. In this study, we generated AMPK-knockdown mice to confirm the EA effect on AMPK activation and further clarify the mechanism of EA in regulating energy metabolism and improving cognitive function in APP/PS1 mice. The behavioral results showed that EA treatment can improve the learning and memory abilities in APP/PS1 mice. At the same time, the glucose metabolism in the hippocampus was increased detected by MRI-chemical exchange saturation transfer (MRI-CEST). The expression of proteins associated with AG in the hippocampus was increased simultaneously, including hexokinase II (HK2), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), and pyruvate kinase M2 (PKM2). Moreover, the knockdown of AMPK attenuated AG activated by EA treatment. In conclusion, this study proves that EA can activate AMPK to enhance the process of AG in the early stage of AD.

scholarly journals Study of the AMP-activated protein kinase role in energy metabolism changes during the postmortem aging of yak longissimus lumborum

2019 ◽  
Author(s):  
Yayuan Yang ◽  
Ling Han ◽  
Qunli Yu ◽  
Yongfang Gao ◽  
Rende Song
Keyword(s):  
Energy Metabolism ◽  
Protein Kinase ◽  
Opposite Effect ◽  
Ph Value ◽  
Physiological Mechanism ◽  
Adenosine Monophosphate ◽  
Postmortem Aging ◽  
Longissimus Lumborum ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

AbstractTo explore the postmortem physiological mechanism of muscle, activity of adenosine monophosphate activated protein kinase (AMPK) as well as its role in energy metabolism of postmortem yaks were studied. In this experiment, we injected 5-amino-1-beta-d-furanonyl imidazole-4-formamide (AICAR), a specific activator of AMPK, and the specific AMPK inhibitor STO-609, to observe the changes in glycolysis, energy metabolism, AMPK activity and AMPK gene expression (PRKA1 and PRKA2) in postmortem yaks during maturation. The results showed that AICAR could increase the expression of the PRKKA1 and PRKAA2 genes, activate AMPK and increase its activity. The effects of AICAR include a lower concentration of ATP, an increase in AMP production, an acceleration of glycolysis, an increase in the lactic acid concentration, and a decrease in the pH value. In contrast, STO-609 had the opposite effect. Under hypoxic adaptation, the activity of the meat AMPK increased, which accelerated glycolysis and metabolism, and more effectively regulated energy production.

Curcumin inhibits aerobic glycolysis in hepatic stellate cells associated with activation of adenosine monophosphate-activated protein kinase

IUBMB Life ◽  
2016 ◽  
Vol 68 (7) ◽  
pp. 589-596 ◽  
Author(s):  
Naqi Lian ◽  
Huanhuan Jin ◽  
Feng Zhang ◽  
Li Wu ◽  
Jiangjuan Shao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Hepatic Stellate Cells ◽  
Aerobic Glycolysis ◽  
Stellate Cells ◽  
Adenosine Monophosphate

scholarly journals An ‘invisible’ ubiquitin conformation is required for efficient phosphorylation by PINK1

2017 ◽  
Author(s):  
Christina Gladkova ◽  
Alexander F. Schubert ◽  
Jane L. Wagstaff ◽  
Jonathan N. Pruneda ◽  
Stefan M.V. Freund ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Dynamic Equilibrium ◽  
Chemical Exchange ◽  
Point Mutations ◽  
Kinase Domain ◽  
Chemical Exchange Saturation Transfer ◽  
Saturation Transfer ◽  
Wild Type ◽  
Functional Studies ◽  
Folded Proteins

ABSTRACTThe Ser/Thr protein kinase PINK1 phosphorylates the well-folded, globular protein ubiquitin (Ub) at a relatively protected site, Ser65. We had previously shown that Ser65-phosphorylation results in a conformational change, in which Ub adopts a dynamic equilibrium between the known, common Ub conformation and a distinct, second conformation in which the last β-strand is retracted to extend the Ser65 loop and shorten the C-terminal tail. We here show using Chemical Exchange Saturation Transfer (CEST) NMR experiments, that a similar, C-terminally retracted (Ub-CR) conformation exists in wild-type Ub. Ub point mutations in the moving β5-strand and in neighbouring strands shift the Ub/Ub-CR equilibrium. This enabled functional studies of the two states, and we show that the Ub-CR conformation binds to the PINK1 kinase domain through its extended Ser65 loop and is a superior PINK1 substrate. Together our data suggest that PINK1 utilises a lowly populated yet more suitable Ub-CR conformation of Ub for efficient phosphorylation. Our findings could be relevant for many kinases that phosphorylate residues in folded proteins or domains.

scholarly journals Tensin links energy metabolism to extracellular matrix assembly

2017 ◽  
Vol 216 (4) ◽  
pp. 867-869 ◽  
Author(s):  
Emmanuel Dornier ◽  
Jim C. Norman
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Energy Metabolism ◽  
Protein Kinase ◽  
Adenosine Monophosphate ◽  
Matrix Assembly ◽  
Cellular Processes ◽  
Metabolic Sensor ◽  
Fibrillar Adhesion ◽  
Α5β1 Integrin

The regulation of integrin function is key to fundamental cellular processes, including cell migration and extracellular matrix (ECM) assembly. In this issue, Georgiadou et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201609066) report that the metabolic sensor adenosine monophosphate–activated protein kinase influences tensin production to regulate α5β1-integrin and fibrillar adhesion assembly and thus reveal an important connection between energy metabolism and ECM assembly.

scholarly journals TRPV1 Activation by Capsaicin Mediates Glucose Oxidation and ATP Production Independent of Insulin Signalling in Mouse Skeletal Muscle Cells

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1560
Author(s):  
Parisa Vahidi Ferdowsi ◽  
Kiran D. K. Ahuja ◽  
Jeffrey M. Beckett ◽  
Stephen Myers
Keyword(s):  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Oxidation ◽  
Transient Receptor Potential ◽  
Insulin Signalling ◽  
Cell Signalling ◽  
Adenosine Monophosphate ◽  
C2c12 Cells ◽  
Atp Production ◽  
Signalling Molecules

Background: Insulin resistance (IR), a key characteristic of type 2 diabetes (T2DM), is manifested by decreased insulin-stimulated glucose transport in target tissues. Emerging research has highlighted transient receptor potential cation channel subfamily V member (TRPV1) activation by capsaicin as a potential therapeutic target for these conditions. However, there are limited data on the effects of capsaicin on cell signalling molecules involved in glucose uptake. Methods: C2C12 cells were cultured and differentiated to acquire the myotube phenotype. The activation status of signalling molecules involved in glucose metabolism, including 5’ adenosine monophosphate-activated protein kinase (AMPK), calcium/calmodulin-dependent protein kinase 2 (CAMKK2), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), protein kinase B (AKT), and src homology phosphatase 2 (SHP2), was examined. Finally, activation of CAMKK2 and AMPK, and glucose oxidation and ATP levels were measured in capsaicin-treated cells in the presence or absence of TRPV1 antagonist (SB-452533). Results: Capsaicin activated cell signalling molecules including CAMKK2 and AMPK leading to increased glucose oxidation and ATP generation independent of insulin in the differentiated C2C12 cells. Pharmacological inhibition of TRPV1 diminished the activation of CAMKK2 and AMPK as well as glucose oxidation and ATP production. Moreover, we observed an inhibitory effect of capsaicin in the phosphorylation of ERK1/2 in the mouse myotubes. Conclusion: Our data show that capsaicin-mediated stimulation of TRPV1 in differentiated C2C12 cells leads to activation of CAMKK2 and AMPK, and increased glucose oxidation which is concomitant with an elevation in intracellular ATP level. Further studies of the effect of TRPV1 channel activation by capsaicin on glucose metabolism could provide novel therapeutic utility for the management of IR and T2DM.

scholarly journals Study of the AMP-activated Protein Kinase Role in Energy Metabolism Changes during the Postmortem Aging of Yak Longissimus dorsal

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 427
Author(s):  
Yayuan Yang ◽  
Ling Han ◽  
Qunli Yu ◽  
Yongfang Gao ◽  
Rende Song
Keyword(s):  
Energy Metabolism ◽  
Protein Kinase ◽  
Opposite Effect ◽  
Ph Value ◽  
Physiological Mechanism ◽  
Adenosine Monophosphate ◽  
Theoretical System ◽  
Postmortem Aging ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

To explore the postmortem physiological mechanism of muscle, activity of adenosine monophosphate activated protein kinase (AMPK) as well as its role in energy metabolism of postmortem yaks were studied. In this experiment, we injected 5-amino-1-beta-d-furanonyl imidazole-4-formamide (AICAR), a specific activator of AMPK, and STO-609 to observe the changes in glycolysis, energy metabolism, AMPK activity, and AMPK gene expression (PRKA1 and PRKA2) in postmortem yaks during maturation. The results showed that AICAR could increase the expression of the PRKKA1 and PRKAA2 genes, activate AMPK and increase its activity. The effects of AICAR include a lower concentration of ATP, an increase in AMP production, an acceleration of glycolysis, an increase in the lactic acid concentration, and a decrease in the pH value. In contrast, STO-609 had the opposite effect. Under hypoxic adaptation, the activity of the meat AMPK increased, which accelerated glycolysis and metabolism and more effectively regulated energy metabolism. Therefore, this study lays the foundation for establishing a theoretical system of energy metabolism in postmortem yak meat.

scholarly journals NIMG-49. VALIDATION OF SIMULTANEOUS PH- AND O2-WEIGHTED MOLECULAR MRI USING 18F-FDG PET, IMMUNOHISTOCHEMISTRY, AND BIOENERGETICS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii158-ii159
Author(s):  
Akifumi Hagiwara ◽  
Jingwen Yao ◽  
Catalina Raymond ◽  
Danielle Morrow ◽  
Sergey Mareninov ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Chemical Exchange ◽  
Aerobic Glycolysis ◽  
Standardized Uptake Value ◽  
Monocarboxylate Transporter ◽  
Oxygen Extraction Fraction ◽  
Chemical Exchange Saturation Transfer ◽  
Monocarboxylate Transporter 1 ◽  
Bioenergetic Analysis ◽  
18F Fdg

Abstract This study aimed to investigate the potential of a novel MRI metric related to aerobic glycolysis in patients with diffuse gliomas. All subjects (Study I–III; 7, 26, and 11 subjects, respectively) were scanned on 3-T systems and underwent pH-weighted amine chemical exchange saturation transfer spin-and-gradient-echo echoplanar imaging (CEST-SAGE-EPI) or CEST-EPI, and perfusion imaging. Relative oxygen extraction fraction (rOEF) was calculated by dividing hypoxia-sensitive R2’ by normalized relative cerebral blood volume (nrCBV); a novel metric that characterizes glycolytic status (aerobic glycolytic index, AGI) was calculated by dividing amine CEST contrast by rOEF. Patients in Study I were additionally scanned by 18F-fluorodeoxyglucose (FDG)-PET. Stereotactic image-guided biopsies were performed on patients in Study II and III, and samples were analyzed by immunohistochemistry (IHC) and extracellular flux bioenergetic analysis, respectively. Pairwise correlation between MR metrics and standardized uptake value of 18F-FDG, IHC metrics, or indices of cellular metabolism was calculated using Spearman’s correlation analysis. In Study I, AGI showed very strong significant correlation with 18F-FDG uptake in glioma (correlation coefficient ρ = 0.86, P =0.014). In Study II, AGI was significantly correlated with glucose transporter 3 (ρ = 0.71; P = 0.0041) and hexokinase 2 (ρ = 0.73; P = 0.0029) in IDH wild-type glioma, while it was significantly correlated with monocarboxylate transporter 1 (ρ = 0.59; P = 0.0094) in IDH mutant glioma. This result may reflect the different glycolytic statuses of these gliomas; specifically, the rate-limiting steps in glycolysis. In Study III, a strong significant correlation with cellular AGI derived from the bioenergetic analysis was found for AGI derived from MRI (ρ = 0.79, P = .036). In conclusion, AGI derived from MRI was correlated with FDG, IHC measurements, and cellular AGI. Future studies investigating the clinical utility of AGI in prediction and evaluation of treatment effects are warranted.

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